探讨北京市孕妇中孕期血清学筛查(STSS)联合孕妇外周血胎儿游离DNA无创产前检测(NIPT)(以下简称为联合筛查)在胎儿唐氏综合征(DS)产前筛查的应用价值。

选择2017年1月至2018年12月，于北京市各产前筛查或诊断机构中(北京妇产医院等)，接受胎儿DS筛查的331 684例单胎妊娠适龄孕妇(预产期年龄<35岁)为研究对象。其中，302 065例孕妇接受STSS，包括20 534例接受联合筛查孕妇；29 619例孕妇自愿直接进行NIPT。对上述孕妇的临床资料进行回顾性分析。采用χ²检验及Mann-Whitney U检验，对3种方法的胎儿DS假阳性率、检出率、阳性预测值及特异度进行总体及两两比较。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。孕妇对所接受的检查项目均知情同意，并签署知情同意书。

①STSS、联合筛查和直接NIPT的胎儿DS假阳性率分别为5.12%、0.07%和0.07%，检出率分别为76.1%、100.0%和93.3%，阳性预测值分别为0.76%、68.75%和56.00%，特异度分别为94.9%、99.9%和99.9%。②联合筛查的胎儿DS检出率、阳性预测值及特异度，均显著高于STSS，而假阳性率，则显著低于STSS，并且上述差异均有统计学意义(Z＝-13.229、P<0.001，Z＝-8.307、P＝0.029，Z＝-13.928、P<0.001，Z＝-7.141、P＝0.038)；联合筛查的胎儿DS检出率及阳性预测值，均显著高于直接NIPT，并且差异均有统计学意义(Z＝-13.856、-11.136，均为P<0.001)；联合筛查与直接NIPT的胎儿DS假阳性率及特异度比较，差异均无统计学意义(均为P>0.05)。

联合筛查对胎儿DS的筛查效率优于STSS和直接NIPT，可降低介入性产前诊断的孕妇比例。

To discuss clinical value of prenatal screening and diagnosis for fetal Down syndrome (DS) of pregnant women in Beijing, which combined second trimester serum screening (STSS) and non-invasive prenatal testing (NIPT) used fetal free DNA in maternal peripheral blood (hereinafter referred to as combined screening).

From January 2017 to December 2018, a total of 331 684 singleton pregnancy women of appropriate age maternal age at expected date of childbirth <35 years who took prenatal screening for fetal DS at various prenatal screening or diagnosis institutions (Beijing Obstetrics and Gynecology Hospital, etc.) in Beijing were selected as research subjects. A total of 302 065 pregnant women who took prenatal screening for DS by STSS, including 20 534 cases took combined screening; 29 619 cases who took prenatal screening for DS voluntarily by direct NIPT. Retrospectively analyzed clinical data of pregnant women. Fetal DS false positive rate, detection rate, positive predictive value and specificity of the three methods were compared overall and pairwise using chi-square test and Mann-Whitney U test. The procedure of this study was in line with World Medical Association Declaration of Helsinki revised in 2013. The pregnant women have informed consent to the inspection items accepted and signed the informed consent form.

① Fetal DS false positive rates by STSS, combined screening and direct NIPT were 5.12%, 0.07% and 0.07%, respectively, the detection rates were 76.1%, 100.0% and 93.3%, respectively, positive predictive values were 0.76%, 68.75% and 56.00%, respectively, specificity were 94.9%, 99.9% and 99.9%, respectively. ②Fetal DS detection rate, positive predictive value and specificity of combined screening were significantly higher than those of STSS, while false positive rate was significantly lower than that of STSS, and the above differences were statistically significant (Z=-13.229, P<0.001; Z=-8.307, P=0.029; Z=-13.928, P<0.001; Z=-7.141, P=0.038). Fetal DS detection rate and positive predictive value of combined screening were significantly higher than those of direct NIPT, and the differences were statistically significant (Z=-13.856, -11.136, both P<0.001). There were no significant differences between combined screening and direct NIPT in fetal DS false positive rate and specificity (both P>0.05).

The efficiencies of prenatal screening for fetal DS by combined screening is better than that of STSS and direct NIPT, which can reduce proportion of pregnant women undergoing interventional prenatal diagnosis.